BIOM 3090 Lecture 27: Local Anesthetics
9 Jun 2018
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Department
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Professor
Local Anesthetics
Local anesthetics
- Derivatives of cocaine that do not produce euphoria
- Inhibit pain without causing unconsciousness
- Esters (R-O-R): short duration because metabolized locally and in blood plasma by
pseudocholinesterase
- Amides: all newer drugs; more stable → longer duration (also easier to overdose)
- Weak bases (B + H+ → BH+)
o Less effective in acidic (inflamed/infected) tissue because can’t cross cell
membranes to reach receptor site on cytoplasmic face of membrane receptor
- Rapid injection is painful (true of any drug)
- Mechanism of action:
o Bind R on cytoplasmic surface of voltage-sensitive Na+ channels
o Block pore → Na+ cannot enter cell
o Inhibits action potential in axons (and skeletal & cardiac myocytes)
o Small fibres (e.g. pain) blocked at lower concentration, motor fibres blocked last
- Analgesics inhibit the generation of pain signals (e.g. opioids)
- Local anesthetics (LA) inhibit the transmission of signals related to all sensations & motor
activity (e.g. lidocaine)
- Vasoconstrictors:
o LAs block channels until they diffuse away
o LAs can be combined with a vasoconstrictor (usually epinephrine)
o Slows removal of drug → prolongs action
o Can delay healing (reduced blood flow)
o Do not use where end-artery supplies organ
▪ Digits, ears, nose, penis, etc. → ischemia → necrosis
o Skin necrosis (i.e. tissue death) can occur when lidocaine + epinephrine are
administered SC
o Some practitioners will not use these products because of this risk
- Systemic effects of locals:
o CNS: as dose increases – initially drowsiness, then excitation +/- seizures
o CVS: decreased excitability of myocardium (SA node, Purkinje system less sensitive)
→ may cause “AV block”, arrhythmias
▪ Rare: cardiac arrest – requires high plasma drug [] (e.g. accidental bolus to
heart)
- Cocaine: isolated 1855; first used as ophthalmic anesthetic in 1884
o Addictive, but only local available until 1904
o Still used topically in >50% of rhinolaryngologic (nose & throat) cases (e.g. TAC –
Topical Anesthetic Solution: Tetracaine-Adrenaline-Cocaine 4%) for exam & repair
of wounds in children
o Applied to oral/nasal mucosa for nose & throat procedures due to excellent
penetration & sympathomimetic action: inhibits NE re-uptake → vasoconstriction
→ less bleeding → easier to see
o Very irritating to tissues; can produce severe CVS toxicity (hypertension,
arrhythmias, cardiac arrest)
- Procaine: synthesized 1905
o Main local anesthetic until lidocaine (1948)
o Problem: an ester, which is cleaved by plasma esterase’s → short duration of action
(15-60 minutes)
o An ester → more allergenic than amides (newer locals)
o Sometimes still used when rapid onset & short duration desired
- Today, Lidocaine is the most widely used local
Document Summary
Derivatives of cocaine that do not produce euphoria. Esters (r-o-r): short duration because metabolized locally and in blood plasma by. Amides: all newer drugs; more stable longer duration (also easier to overdose) Weak bases (b + h+ bh+: less effective in acidic (inflamed/infected) tissue because can"t cross cell membranes to reach receptor site on cytoplasmic face of membrane receptor. Rapid injection is painful (true of any drug) Analgesics inhibit the generation of pain signals (e. g. opioids) Local anesthetics (la) inhibit the transmission of signals related to all sensations & motor activity (e. g. lidocaine) Ischemia necrosis: skin necrosis (i. e. tissue death) can occur when lidocaine + epinephrine are administered sc, some practitioners will not use these products because of this risk. Systemic effects of locals: cns: as dose increases initially drowsiness, then excitation +/- seizures, cvs: decreased excitability of myocardium (sa node, purkinje system less sensitive)
